Study to Evaluate the Efficacy and Safety of EP-104IAR in Patients With Osteoarthritis of the Knee

This is a randomized, double-blind, placebo-controlled, single injection, 24-week study to evaluate the safety, efficacy and PK of EP-104IAR in subjects with osteoarthritis knee pain

Following screening and baseline assessments to determine eligibility, each participant will receive a single IA injection of either EP-104IAR or placebo (vehicle). Participants will be followed up for 24 weeks following the injection for safety, PK and efficacy assessments.

Key Inclusion Criteria:

• Males or females, aged ≥40 years
• Body Mass Index (BMI) ≤ 40.0 kg/m2
• Diagnosis of primary OA of the Index knee, with symptoms present for at least 6 months
• OA severity Grade 2 or 3 (based on Kellgren Lawrence Grading Scale)
• Unsatisfactory pain relief from at least 2 prior standard OA treatments
• Qualifying pain in the Index knee during the baseline period
• Ambulatory (without the need for a cane/other walking aide)
• Female subjects willing to use highly effective birth control methods to prevent pregnancy
• Willing and able to comply with study procedures and restrictions, including abstaining from use of restricted medications.

Key Exclusion Criteria:

• OA of the Index knee due to acute injury or trauma, or unstable joint
• X-ray evidence of chondrocalcinosis
• Diagnosed or suspected ipsilateral hip OA
• Knee pain that is not attributable to OA of the knee
• Any other disorders that impact mobility, strength or sensation, or are a co-existent source of pain or inflammation that interfere with assessment of knee pain and function
• History of infection in the Index knee
• Skin breakdown on the Index knee where the injection will take place
• Total Knee Replacement, or any other surgery (including arthroscopy) for the Index knee within prior 12 months, or planned surgery during the study
• Total Knee Replacement Surgery of the non-Index knee within prior 6 months, or planned surgery (any location) during the study that would require a restricted medication
• IA injection of corticosteroids in any joint within prior 3 months or IA injection of extended-release corticosteroids in any joint within prior 6 months
• IA injection in the Index knee of platelet rich plasma, or other prolotherapy within prior 3 months, or hyaluronic acid within prior 6 months
• Recent, current or planned use of corticosteroids for any indication (except for permitted uses)
• Recent, current or planned use of prohibited medications (including analgesics, marijuana, investigational drugs and devices, immunosuppressive therapy), or unwilling or unable to stop using prohibited medications during the study.
• Conditions including: sarcoidosis, amyloidosis, osteomyelitis, Cushing's Syndrome, hepatic or renal disease, Psychotic disorder, bipolar disorder, symptomatic depressive or anxiety disorders.
• Current malignancy of any type, or history of a malignancy within prior 12 months
• Active or quiescent systemic fungal, bacterial (including tuberculosis) viral (including HIV, Hepatitis B or C) or parasitic infections, or ocular herpes simplex, or any recent infection requiring IV or oral antibiotics
• Laboratory results indicative of adrenal insufficiency, diabetes or renal or hepatic disease.
• Positive urine drug screen for a substance of abuse
• Females who are pregnant, lactating
• Known or suspected hypersensitivity or contraindication to ingredients in the study drug